A New Lipid Based Drug Delivery System (LBDDS) for Oral Delivery of Tioconazole

anthony attama, igwebuike ayogu, franklin kenechukwu, john ogbonna, vincent okore

Abstract


Purpose: Peroral delivery of some drugs with limited aqueous solubility has remained a challenge to drug formulation experts. This work seeks to address the issue of unavailability of oral delivery system of tioconazole, a potent antifungal agent.

Method: Novel lipid based drug delivery systems (LBDDS) of tioconazole, composed of oil, surfactants and co-surfactants were  formulated and  their physicochemical as well as pharmacokinetic parameters determined. The oil, surfactant and co-surfactant used were soya bean oil, Cremophor® S9 and Brij® 35, respectively. The droplet sizes of the tioconazole micro-emulsion obtained after self emulsification were assessed after 72 h incubation. The in vitro permeation studies of the tioconazole-loaded LBDDS were evaluated using a modified Franz cell.

Result: Permeation  coefficients of the formulation were between 1.204 x 10-3 cm/sec and 2.178 x 10-3 cm/sec. In vitro microbiological test of the tioconzole LBDDS revealed increased in vitro antifungal activity (≈ 1.4 times) against clinically isolated Candida albicans as compared to tioconazole solution. Preliminary in vivo pharmacokinetic studies also showed an AUC∞-12 of 2930 µg/hr/ml for the optimized LBDDS formulation while that of oral suspension was 1171 µg/hr/ml and the  Cmax of the optimized LBDDS formulation was 797 µg/ml  as against 355 µg/ml obtained for the pure drug. This showed a 2.5-fold increase in the systemic bioavailability of tioconazole from the optimized LBDDS formulation.

Conclusion: The result of this study gave insight that the issue of unavailability of tioconazole in oral delivery system could be surmounted by tactical engineering of  LBDDS such as self-microemulsifying drug delivery systems (SMEDDS).


Keywords


tioconazole; bioavailability; LBDDS; Cremophor®S9; Brij®35; permeation coefficient.

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References


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